Should Exercisers Lay off the Antihistamines?

Pollen levels are high and you have a 10-K run ahead of you. Do you pop a couple of antihistamines to avoid an allergic reaction? Or not?

Sorry, a definitive answer is not provided here.

However, a newly published study from the UO lab of John Halliwill has raised such questions. The research found that 795 (about 27 percent) of 3,000 genes activated after vigorous exercise become blunted in their responses during a three-hour recovery period if exercisers had taken strong doses of antihistamines.

Halliwill, a professor in the Department of Human Physiology, discovered in 2005 that naturally occurring histamines in the body relax blood vessels, increasing blood flow that aids post-exercise recovery. That emerged from his original focus on why some people, including athletes, pass out after vigorous physical exertion. He later found a link between an overactivation of two histamine receptors to drops in blood pressure.

The new study — led by doctoral student Steven A. Romero and in collaboration with Hans Dreyer, a departmental colleague who studies muscle physiology — expanded the research to a wider genetics level. Researchers sequenced RNA, molecules essential for making proteins and sending signals among genes, with state-of-the-art equipment in the UO's Genomics Core Facility.

"We were looking for pathways associated with the growth of new blood vessels," said Halliwill, director of the Exercise and Environmental Physiology Lab. "We saw evidence of that, but we also saw gene expression associated with glucose uptake by muscles, restructuring of muscle in response to exercise, immune responses and intercellular communications."

In the research, 16 physically fit and active young adults performed an hour of knee-extension exercise at a pace of about 45 kicks per minute. Biopsies were done before exercise and three hours after to obtain samples from the quadriceps, the skeletal muscles on the side of the thighs.

Eight participants took 540 milligrams of fexofenadine (Allegra) and 300 milligrams of ranitidine (Zantac) at nearly three times the recommended dosages of the over-the-counter antihistamines. Together they target the two histamine receptors involved in both allergic reactions and exercise-recovery responses.

Blood flow, blood pressure and heart rate were monitored during the exercise. During the three-hour recovery window the research team was able to study early signs of gene expression; they found that 88 percent of the 795 genes affected by the antihistamines mostly responded with lower levels of expression.

"Histamine, a substance that we typically think of negatively and is most often associated with seasonal allergies, is an important substance contributing to the normal day-to-day response to exercise in humans," said Romero, who is now at the University of Texas Southwestern Medical Center in Dallas on a postdoctoral fellowship from the National Institutes of Health.

In their conclusion, the 10 co-authors noted that the research highlighted only a small fraction of genes likely involved in signaling pathways influenced by the activation of histamine receptors during recovery.

A key question is whether people should avoid taking antihistamines when they exercise. It's too early to make that call, Halliwill said. For now, he said, people should use their own judgment about choosing to take or avoid antihistamines when performing when they know they will be exposed to allergens.

"There are a lot of redundancies in physiological systems," he said. "I wouldn't be surprised if blocking histamine receptors ends up being overcome by something else, but I also wouldn't be surprised if we can demonstrate that some responses to exercise training do become blunted if you take high doses of histamine blockers."

The study is now online ahead of print in the Journal of Physiology. The NIH and American Heart Association supported the research.